UST, pregnancy & infant health

February 26, 2024

Issue 05

Clinical Question

Does ustekinumab during pregnancy increase infant health risk?

Editor’s Bottom Line

These data provide additional reassurance about the safety of biologic therapies for inflammatory bowel disease during pregnancy, with no detectable increase in adverse infant outcomes after ustekinumab exposure.

Reference

Julsgaard M, Wieringa JW, Baunwall SMD, et al. Infant ustekinumab Clearance, Risk of Infection, and Development after exposure during pregnancy. Clin Gastroenterol Hepatol. Epub ahead of print Jan 24, 2024; https://www.cghjournal.org/article/pdf

Synopsis

Researchers at 19 outpatient IBD clinics in Denmark and the Netherlands analyzed data from 78 live births in 76 women exposed to ustekinumab during pregnancy between 2018 and 2022. They documented infant infection rates requiring hospitalization or antibiotics, developmental milestones, and cord and serum ustekinumab concentrations at the time of labour.

Most women received the agent at 8-week intervals and 80% initiated treatment prior to conception. Among the 20% of women who started treatment during pregnancy, an intravenous induction dose was administered after a median 14 gestational weeks, with roughly half receiving the induction dose during the second trimester and one patient receiving an induction dose during the third trimester. Most women received treatment for the duration of their pregnancy.

Fifty-eight percent of women had active disease despite treatment. Women with ulcerative colitis were 65% more likely to have active disease during pregnancy than those with Crohn’s disease.

Data revealed that 8% of infants were born with a malformation and 9% of infants were born preterm. The median infant birthweight among the 13% of women who discontinued ustekinumab treatment prior to their third trimester was 515 grams lower than for those who continued treatment throughout (p=0.007).

The median infant-to-mother ustekinumab concentration ratio at birth was 2.18 (95% Confidence Interval [CI], 1.69–2.81). Cord and maternal ustekinumab concentrations at birth were a median 3 and 1.4 micrograms/mL, respectively. Disease activity was not associated with median ustekinumab concentrations in maternal blood at the time of delivery.

The mean time to infant clearance of ustekinumab was 6.7 months (95% CI, 6.1–7.3 months), with an estimated mean half-life of 23.2 days after birth (95% CI, 21.5–24.9 days).

Twelve percent of infants had a serious infection requiring hospitalization, with hospitalization occurring a median two months after birth (Range: 0–6 months). Twenty-three percent of infants developed at least one infection requiring antibiotic treatment during the first year of life.

Exposure to induction treatment, ustekinumab exposure during the third trimester or infant ustekinumab concentrations at birth were not associated with a higher risk of adverse outcomes or infant infection. There was no association between breastfeeding and risk of infection.

Of the 82% of infants assessed up to one year, 91% met normal developmental milestones.

Details

Study Design: Prospective cohort
Funding: The Medicine Fund of the Danish Regions, the Danish Crohn’s and Colitis Foundation, and the A.P. Moeller Foundation of the Advancement of Medical Science
Allocation: None
Setting: Multicenter
Level of Evidence: 2b